Diabetes

Question 1

What is the relationship between diabetes mellitus and insulin?

Answer 1

Diabetes mellitus is a relative/absolute insulin deficiency

Question 2

What effect does diabetes mellitus have on metabolism?

Answer 2

It causes:
A Decrease in tissue utilisation of glucose
An increase in tissue utilisation of amino acids and fatty acids
An increase in hepatic glycogenolysis
An increase in hepatic gluconeogenesis

Question 3

What is the difference between type 1 and type 2 DM?

Answer 3

Type 1: beta–cell destruction, usually leading to absolute insulin deficiency, is immune mediated.

Type 2: may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance

Question 4

Do most dogs have IDDM or NIDDM?

Answer 4

Insulin dependant diabetes mellitus

It is a permanent insulin deficiency and the animal needs exogenous insulin.

Question 5

What causes NIDDM?

Answer 5

This is common in cats and caused by obesity and rare in dogs although caused by insulin antagonism and drugs

Question 6

What dog breeds are susceptible to DM?

Answer 6

Samoyed, Terriers and miniature schnauzer.

Question 7

What are the common causes of DM in dogs?

Answer 7

1. Immune-mediated (T cell) destruction of β cells
2. Pancreatitis with β cell destruction
3. Specific hormones antagonise insulin action
4. Genetic suceptibilty
5. Obesity-induced insulin resistance
6. Insulin-antagonistic disease/ conditions
7. Insulin-antagonistic drugs

Question 8

How does Immune-mediated (T cell) destruction of β cells cause DM?

Answer 8

Autoantibodies against insulin and/or beta cells
Destruction of beta-cells
Progressive decrease in glucose-stimulated insulin secretion

Question 9

What hormones antagonise insulin action?

Answer 9

Cortisol and growth hormone Induce peripheral insulin resistance

Question 10

Name an Insulin-antagonistic drug

Answer 10

glucocorticoids

Question 11

What are the common causes of DM in cats?

Answer 11

1. Obesity-induced insulin resistance
2. Islet amyloidosis (similar to what humans will get)
3. Pancreatitis
4. Insulin-antagonistic drugs
5. Insulin-antagonistic disease eg. acromegaly
6. Genetics

Question 12

Define insulin resistance

Answer 12

The diminished ability of cells to respond to the action of insulin in transporting glucose from the blood into tissues

Question 13

What is the effect of insulin resistance on cells?

Answer 13

Inadequate number of insulin receptors
Defective insulin receptor structure
Defective GLUT4 transport proteins
Problems with translocation of GLUT4 to the membrane
Interference with the function of GLUT4

Question 14

In the feline pancreas what is co secreted with insulin by the beta cells? What causes its increased secretion?

Answer 14

Islet amyloid polypeptide or amylin

Chronic increased secretion occurs with obesity and insulin resistant states

Question 15

How does amylin cause defective insulin secretion?

Answer 15

Amylin deposited in the islets as amyloid and amyloid fibrils are cytotoxic, so apoptosis of islet cells occurs and leads to defective insulin secretion

Question 16

What is the clinical presentation of DM?

Answer 16

Polyuria/polydipsia
Polyphagia
Weight loss
Cataracts
Ketoacidosis

Question 17

Why do animals with DM have PU?

Answer 17

Blood glucose exceeds “renal threshold” so glucose enters the urine.
The glucose acts as an osmotic particle and draws water into the renal tubule, it dilutes the urine and increases urine volume causing osmotic diuresis.

Question 18

Why do animals with DM get polyphagia?

Answer 18

In normal animals the influx of glucose into the hypothalamic satiety centre decreases hunger and so the animal takes in less glucose
In animals with diabetes mellitus there is a lack of insulin so glucose cannot enter the satiety centre, failure to inhibit the appetite centre so the animal has polyphagia despite hyperglycaemia

Question 19

Why do animals with DM get weight loss?

Answer 19

The entry of glucose into the cells is mediated by insulin which DM dogs lack, this leads to a decrease in peripheral tissue utilisation. This Insulin:Glucose ratio falls and promotes starvation mode so the amino acids are broken down and used for gluconeogenesis which is what causes muscle wastage.

Question 20

Why do animals with DM get cataracts?

Answer 20

Glucose is taken up into the lens where it is normally metabolised to lactate which can diffuse out. This excess glucose is converted to fructose and sorbitol that do not diffuse out, this makes the lens take on water via osmosis.

Question 21

Why do animals with DM get ketoacidosis?

Answer 21

Because glucose does not enter the cells very easily the animal mobilises its fat stores and breaks down the fatty acids, this breakdown of fatty acids causes a build up of ketones. This build up leads to metabolic acidosis.

Question 22

How can we diagnose DM?

Answer 22

Hyperglycemia even when fasting
Persistent glucosuria
Fructosamine is a reflection of previous 2-3 weeks of blood glucose so it will be high (but not affected by stress)
Urinalysis will have high specific gravity